The broad and long term goal of the Animal Models Core is provide consistent care, experimental procedures, and husbandry are important to the success ofthe projects. Each promising investigator has limited animal experimental experience, but needs to verify in vitro findings in vivo. Therefore, the Animal Model Core (AMC) will ensure project experimental consistency, compliance with federal animal welfare regulations, and effective training of project leaders and personnel in animal experimentation. Dr. Hinsdale will serve as the AMC director, and along with technical staff will provide basic services (e.g. Colony management and husbandry, biosafety containment and housing of animals, infection of animals and harvesting of samples for analyses, and pulmonary function tests). The current experimental animal models will be mice. The four projects that are proposed require mice to further verify in vivo findings arising from the proposed in vitro experiments. In project 1, using some remarkable viral strains, BALB/c mice will be used to determine the role of the human Respiratory Syncytial Virus (RSV) Matrix protein in viral infection. In project 2, influenza infected mice will be used to validate important host factors in an innovative in vitro respiratory model. In project 3, using a novel mouse model of acute lung injury, challenged mice will be used to mechanistically explore the exciting and potential therapeutic role of a unique protein on acute bacterial lung injury. In project 4, mice will be used to determine mechanistically the pathogenic role that specific chemokine and cytokine mediators have in acute lung injury due to influenza and to determine the pioneering therapeutic combinations for ameliorating this acute lung injury. In all, the up-and-coming young investigators of this application will be breaking new ground in pulmonary disease and gaining important animal model training to prepare them for promising independent research careers.